Biomedical subjects

E Goldin

Publications and source records attributed to E Goldin.

At least 73 records · Page 4Linked to original sources

PubMed1993

Expression of HLA class I antigens in sporadic adenomas and histologically normal mucosa of the colon.

The loss of HLA antigens by neoplastic cells is considered important for tumor growth and metastasis, inasmuch as it may allow tumors to escape immune surveillance. We have observed reduced expression of HLA antigens in sporadic colon cancer and adenomas from familial adenomatous polyposis patients. We now studied the expression of HLA class I antigens in patients with sporadic adenomas, which are precursors of colorectal cancer. Expression of HLA class I antigens was studied by immunohistochemistry in (a) sporadic colon adenomas, (b) histologically normal mucosa distant from the adenomas, (c) histologically normal colonic mucosa from patients with history of sporadic colon adenomas, and (d) colonic mucosa from normal subjects. HLA class I antigen expression was moderately reduced in 56% and severely reduced in 44% of the adenomas; this reduction was significant when compared to controls (P < 0.0001). The reduction of HLA class I expression in adenomas was related to the grade of dysplasia of the adenomas. HLA class I expression of normal appearing mucosa was decreased in 76% of patients with adenoma (P < 0.0001) and in 54% of patients with history of adenoma (P < 0.005) compared to normal controls. These changes were antigen specific, inasmuch as the expression of carcinoembryonic antigen, a surface antigen, was not affected. Our findings suggest that reduced HLA class I expression is an early event in the cell transformation process from normal to neoplastic state, preceding in many cases the onset of histological changes. HLA class I could be potentially used as a premalignant marker in the colon.

Adenoma↗

PubMed1993

Linkage of Niemann-Pick disease type C to human chromosome 18.

We analyzed the involvement of chromosome 18 in Niemann-Pick disease type C (NPC), an autosomal recessive cholesterol-processing disorder. Within affected offspring, the chromosome 18 parental contributions were identified by using allele-specific microsatellite markers. Significant linkage of NPC to an 18p genomic marker, D18S40, was indicated by a two-point lod score of 3.84. Analysis of meiotic chromosomal breakpoint patterns among the affected individuals indicated that the NPC gene is pericentromerically localized on human chromosome 18.

Chromosomes, Human, Pair 18↗

PubMed1993

[Rubber-band ligation of esophageal and cardiac varices].

Esophageal sclerotherapy was the treatment of choice for bleeding esophageal varices in the past decade. It is effective for treating acute variceal bleeding, as well as eradicating esophageal varices for secondary prevention of bleeding. However, in more than 20% of patients sclerotherapy involves complications, some of which are serious. The high complication rate suggested the development of a new method that should be at least as effective and as easy to perform as sclerotherapy, but with fewer complications and side-effects. Endoscopic variceal ligation was developed at the University of Colorado and described in 1986. It is reported to control active variceal bleeding in about 90% of patients, and to eradicate varices in about 80% of surviving patients. Complications are rare. We have adapted the method in our unit and here describe out preliminary experience in 11 patients.

Esophageal and Gastric Varices↗

PubMed1993

A new self-expandable and removable metal stent for biliary obstruction--a preliminary report.

We report our experience with a new self expandable metallic stent, a coil spring made from a nickel-titanium alloy. The super elastic characteristic of this metal offers a very strong radial force and previous dilatation of biliary strictures is not necessary. The stent is endoscopically inserted constricted over an introducing catheter, expanding spontaneously after release to its original 8 mm diameter. During the last six months, eleven stents were inserted in nine patients with pancreatic carcinoma to relieve jaundice. Another stent was percutaneously implanted treating a benign stricture in a patient with a choledochojejunostomy after a Whipple operation. Clinical improvement was achieved in all the patients except in one who died from liver metastases 5 weeks later. In two patients, although stents were obstructed after 2 and 4 months from insertion, they were easily removed by pulling their distal end through the endoscopic working channel. After a mean follow up of 4.5 months, patients had no evidence of biliary reobstruction. Although follow-up is short, these results are encouraging, and this new metallic stent seems to have several advantages over the current commercially available ones.

Aged↗

PubMed1993

Biliary and colonic cutaneous fistula successfully treated by endoscopic insertion of biliary stents.

We report a case in which a large, postoperative cutaneous biliary and a colonic fistula were successfully treated by means of endoscopic insertion of two endoprostheses into the common bile duct. Twenty-four hours after the procedure, bile flow through the leak ceased completely while the colonic fistula closed in 6 days. Six months after the treatment, when a new endoscopic cholangiography showed no evidence of leak or stricture, the stents were removed. For the treatment of postoperative biliary leaks, insertion of endoprostheses is a good and safe alternative to surgery.

Adult↗

PubMed1993

Combined transhepatic and endoscopic procedures in the biliary system.

Endoscopic biliary procedures are 89-97% successful in skilled hands. The commonest causes of failure are inability to cannulate the papilla of Vater due to difficult anatomy or tortuosity of the distal common bile duct and failure to cross a rigid biliary stricture. In nearly all of these cases, successful endoscopic procedures can be completed after percutaneous antegrade placement of a small catheter or guidewire to the duodenum. In 44 such combined procedures on 42 patients, the success rate was 43 (98%). There were two severe and eight mild complications. Combined procedures overcome the difficulties caused by tortuous biliary ducts and rigid strictures while obviating the need for more extensive percutaneous procedures and transhepatic tract dilatation.

Adult↗

PubMed1993

Sclerosing cholangitis associated with Crohn's disease and autoimmune haemolytic anaemia.

A middle-aged man was found to have autoimmune haemolytic anaemia. Seven years after the first manifestations of the anaemia, he developed jaundice without haemolysis and a diagnosis of primary sclerosing cholangitis was made by endoscopic retrograde cholangiography. Crohn's colitis was later confirmed by X-rays and colonoscopy. This association is unique to the best of our knowledge and suggests that genetic and immunological mechanisms may be involved in the pathogenesis of these diseases.

Adult↗

PubMed1993

The murine Niemann-Pick type C lesion affects testosterone production.

We have determined the effects of the Niemann-Pick type C (NPC) lesion, which impairs transport of cholesterol from lysosomes, on the androgenic status of male NPC mice. The mice have low serum testosterone levels resulting from decreased testosterone secretion. Testosterone secretion is reduced in NPC mouse testes incubated with 8-bromo-cAMP, 20 alpha-hydroxycholesterol, and pregnenolone compared to testosterone release by normal mouse testes under identical conditions. Ultrastructural examination of testes revealed a paucity of lipid droplets, extensive accumulation of inclusion bodies, and distorted endoplasmic reticulum in Leydig cells of adult NPC mice. The hypoandrogenemia caused systemic deficiencies in NPC mice. Seminal vesicles, a testosterone-responsive tissue, were underdeveloped in NPC male mice. The testosterone-responsive kidney beta-glucuronidase activity was also underexpressed. Seminal vesicle mass and beta-glucuronidase activity were increased by testosterone treatment of NPC mice. Many hepatic proteins, identified by microsequencing, were also deficient in NPC male mice. Levels of alpha 2-mu-globulin, glutathione S-transferase-pi, carbonic anhydrase-III, and selenium-binding protein increased in normal male mice during puberty, but did not increase in the NPC male mice. Based on the increases in protein expression during puberty, differential expression in males and females, and the reported involvement of androgens in regulating expression of some of these proteins, deficient expression of most of these proteins in male NPC mice appears to result from low testosterone levels. We conclude that a defect in testicular testosterone production in NPC male mice causes a pleiotropic deficiency in androgen-sensitive expression of proteins in various organs.

Aging↗

PubMed1993

Substance P levels in the rectal mucosa of diabetic patients with normal bowel function and constipation.

Substance-P content in rectal mucosa was determined by radioimmunoassay in 28 diabetic patients (17 with severe chronic constipation and 11 with normal bowel function), 24 non-diabetic patients with severe functional constipation, and 27 normal controls. Substance-P content (pg/mg) in the rectal mucosa of diabetics with normal bowel function was significantly higher than that of non-diabetic controls (p < 0.001). Substance-P content in the rectal mucosa of diabetics with constipation was more than double that of patients with non-diabetic functional constipation (p < 0.01) and lower than that of diabetics with normal bowel function (p < 0.0375). Diabetic patients (constipated and non-constipated) have higher substance-P content in the rectal mucosa than non-diabetics. Lower substance-P rectal mucosa content in constipated diabetic patients than in non-constipated diabetics supports a possible role of substance P in the pathogenesis of diabetic constipation.

Adult↗

PubMed1992

Progesterone blocks cholesterol translocation from lysosomes.

Fluorescent microscopic examination of fibroblasts cultured with low density lipoprotein (LDL) and progesterone (10 micrograms/ml) for 24 h revealed extensive filipin-cholesterol staining of perinuclear lysosomes. Levels of unesterified cholesterol were 2-fold greater than in fibroblasts cultured with LDL alone. Progesterone strongly blocked cholesteryl ester synthesis. When cellular uptake of LDL was monitored in the presence of 58035, a specific inhibitor of acyl-CoA:cholesterol acyltransferase, excess unesterified cholesterol was not stored in lysosomes. Discontinuation of LDL uptake in conjunction with progesterone washout markedly reversed the filipin-cholesterol staining of lysosomes. Reversal of the lysosomal cholesterol lipidosis was associated with a rapid burst of cholesteryl ester synthesis and a normalization of the cellular levels of free and esterified cholesterol. In contrast to normal cells, progesterone removal from Niemann-Pick C fibroblasts did not reverse the lysosomal cholesterol accumulation of these mutant cultures. The metabolic precursor of progesterone, pregnenolone, also induced extensive accumulation of cholesterol in lysosomes. Other steroids induced less vacuolar cholesterol accumulation in the following decreasing order: corticosterone and testosterone, promegestone, RU 486. The relative inhibition of cellular cholesterol esterification by the steroids paralleled their respective abilities to sequester cholesterol in lysosomes rather than their inhibition of acyl-CoA:cholesterol acyltransferase activity in cell-free extracts. The progesterone-related inhibition and restoration of lysosomal cholesterol trafficking is a useful experimental means of studying intracellular cholesterol transport. A particularly important feature of its utility is the facile reversibility of the steroid-induced block. The lysosomal cholesterol lipidosis established with a hydrophobic amine, U18666A, was not as readily reversed.

Androstenes↗

PubMed1992

Type C Niemann-Pick disease: a murine model of the lysosomal cholesterol lipidosis accumulates sphingosine and sphinganine in liver.

We have determined the levels of free sphingoid bases in livers of normal and cholesterol lipidotic Niemann-Pick type C mice. Hepatic sphingosine and sphinganine levels in affected mice (593 pmol/mg protein) were elevated more than 20-fold when compared to levels in age-matched normal mice (26 pmol/mg protein). Upon fractionation of mutant liver homogenates by differential centrifugation, most of the sphingoid bases sedimented with beta-hexosaminidase in the 9000 x g pellet. Co-sedimentation of sphingoid bases with a lighter beta-hexosaminidase peak in Percoll gradients suggests that these bases accumulate in lipid laden lysosomes. A cytosolic sphinganine kinase is the first enzyme in the degradative pathway of sphingoid base metabolism. Activity of this enzyme was partially deficient in crude mutant liver cytosolic extracts due to the presence of an inhibitory substance. Following molecular sieving of mutant cytosolic extracts on Sepharose 4B, sphinganine kinase, with normal levels of activity, was resolved from a complex higher-molecular-weight inhibitor fraction. The Km values for either sphinganine or ATP-Mg substrates with partially purified sphinganine kinase from normal and mutant mouse liver extracts, were similar. These findings indicate that accumulation of free sphingoid bases is not due to a direct inherent deficiency in the catalytic activity of sphinganine kinase. The possible cause and effect relationship between the accumulation of these endogenous hydrophobic amines and the lesion in intracellular cholesterol trafficking in Niemann-Pick type C disease is discussed.

Animals↗

PubMed1992

Niemann-Pick type-C disease: deficient intracellular transport of exogenously derived cholesterol.

NPC disease is an autosomal recessive neurovisceral storage disorder. A pleiotropic array of secondary enzymatic and storage abnormalities has in the past obscured a cohesive understanding of the underlying metabolic basis of this disorder. Recent findings, reviewed in this report, demonstrate that NPC disease is a cholesterol lipidosis resulting from defective intracellular cholesterol transport. The sequence of cellular events characteristic of NPC is 1) deficient intracellular transport of exogenously derived cholesterol resulting in retarded induction of cellular cholesterol homeostatic regulation; 2) accumulation of cholesterol in lysosomes; and 3) secondary cellular effects. Retarded esterification of exogenous cholesterol and accumulation of unesterified cholesterol in lysosomes is tightly coupled to the primary defect and serves as the basis for biochemical diagnosis of NPC.

Antigens, CD↗

PubMed1992

Pancreatitis in ulcerative colitis.

A 19-year-old man without apparent predisposing factors was found to have chronic pancreatitis and 6 months later developed ulcerative colitis. Is there a real association between pancreatitis and inflammatory bowel disease? We discuss previous reports.

Adult↗

PubMed1992

Serological and molecular analysis of HLA in Israeli primary sclerosing cholangitis patients.

HLA class I and class II were investigated in 15 Israeli primary sclerosing cholangitis patients and compared to healthy controls. None of the well established serological specificities were found to be associated with the disease. HLA-DR52 is serologically defined, but its subtypes DR52a, DR52b, and DR52c cannot be precisely defined by serological means. Therefore, we have used HLA-DNA typing in order to assign the DR52 splits in PSC patients. Genomic DNA was amplified by PCR, dot-blotted and hybridized with sequence specific oligonucleotide probes defining the known HLA-DR52 associated alleles. Only 4 out of the 15 PSC patients tested were found to express DRB3*0101 the allele that encodes DR52a. Of the remaining 11 patients, 9 expressed DRB3*0202 haplotypes, with 2 patients expressing both DRB3*0101 and DRB3*0202, and the remaining 2 patients expressed no DRB3 allele. Our data indicate that there is no apparent association between PSC and the HLA antigens and alleles studied including the alleles of the DRB3 locus in the Israeli population. Thus HLA pheno/genotyping of PSC patients in the Israelis will not be useful for early and/or differential diagnosis of this disease.

Alleles↗

PubMed1992

Palliation of malignant bile duct obstruction: our experience with endoscopic 14 French prostheses.

We evaluated the efficacy of wide 14F endoprostheses endoscopically placed in en patients with malignant extrahepatic bile duct stenosis. Large-bore stents were successfully placed in all patients. There were no early complications. Stent clogging occurred in two patients after one month and after three months in another patient. Seven patients remained free of symptoms after a mean follow-up period of 4.5 months.

Aged↗

PubMed1992

Seasonal fluctuations in acute upper gastrointestinal bleeding: lack of effect of nonsteroidal anti-inflammatory drugs.

The seasonal pattern of community-based acute bleeding from the upper gastrointestinal (UGI) tract was studied prospectively in 1988-1991. Out of 3343 emergency admissions to the Departments of General Surgery, 321 (9.6%) were due to acute UGI bleeding. There was a significant monthly variation in the total number of admissions, as well as in the number of admissions due to acute UGI bleeding (p < 0.0001). However, there was no correlation between the two. Significant seasonal fluctuations were noted both in the absolute number of admissions due to acute UGI bleeding and in the percentage of UGI bleeding admissions of the total number of admissions to the Departments of General Surgery (p = 0.0002). During summer (July through September), the incidence declined significantly to a nadir of 5.5% of total number of admissions in July. The seasonal fluctuation correlated closely with the incidence of duodenal ulcer, but not with that of gastric ulcer. The seasonal pattern was consistent both in patients who had used aspirin or other nonsteroidal anti-inflammatory drugs as well as in those who had not.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1991

Type C Niemann-Pick disease: cellular uncoupling of cholesterol homeostasis is linked to the severity of disruption in the intracellular transport of exogenously derived cholesterol.

A uniquely attenuated disruption of cholesterol homeostasis has been characterized in certain Niemann-Pick, type C (NP-C) fibroblasts. Uptake of LDL-cholesterol by cultured fibroblasts derived from two clinically affected brothers with this variant biochemical phenotype led to less intracellular accumulation of unesterified cholesterol than found in other typical cell lines. This limited cholesterol lipidosis in the variant NP-C cells reflected cholesterol processing errors that differed from the cellular lesions in classical NP-C cells in the following ways: (1) a more limited intracellular distribution of the excessive unesterified cholesterol; (2) shorter and more transient delays in the induction of cholesterol-mediated homeostatic responses; and (3) more efficient intracellular transport of exogenously derived cholesterol to the plasma membrane and the endoplasmic reticulum. Activation of acyl-CoA cholesterol acyltransferase (ACAT) was greater than 100-fold in both control and NP-C fibroblasts when cell cultures were preconditioned with 25-hydroxycholesterol, but the subsequent esterification of exogenous non-lipoprotein [3H]cholesterol remained deficient in all NP-C cells. In the variant NP-C cells conditioned with the oxysterol, this esterification of exogenous [3H]cholesterol was less affected than in classical NP-C cultures. The NP-C mutation affects a broad spectrum of metabolic responses related to the processing of exogenously derived cholesterol. Among this pleiotropic array of deficient responses, retarded intracellular cholesterol transport appears most closely linked to the primary mutation. This conclusion is supported by two current observations: (1) the degree to which sterol transport is affected in mutant cells in turn reflects the extent to which cholesterol-homeostatic responses are compromised; and (2) sterol transport remains deficient despite concurrent normal activation of other cellular responses, such as cholesterol esterification.

Adult↗

PubMed1991

Idiopathic gastroparesis in patients with unexplained nausea and vomiting.

Nausea and vomiting are symptoms sometimes associated with motor dysfunction. We compared a group of young patients suffering from chronic nausea and/or vomiting and normal upper gastrointestinal x-ray series with a control group. The members of both groups underwent isotopic examinations of their stomachs. The aim of the study was to find a simple method of checking the stomach and proving a motor dysfunction in a group of patients with chronic, inexplicable nausea and vomiting. Patients and controls fasted for at least 6 hr were given 0.5 mCI of [99mTc] diethylene triaminopentaacetic acid orally in 150 cc milk with 50 g cornflakes. A time-activity curve was obtained and radioactivity over the stomach was recorded exponentially. The parameter of the T1/2 emptying time was used. In normal controls T1/2 emptying time ranged from 18 to 26 min. Twenty-five symptomatic patients were examined, three of whom achieved normal values, but 22 patients showed pathologic results ranging from 36 to 184 min. In patients with chronic nausea and/or vomiting an isotopic examination of the stomach may provide a simple and rapid diagnostic method of evaluation.

Adult↗